DESCRIPTION: (Applicant's Abstract) We propose to study viral, immunologic and genetic factors related to HIV infection and disease progression in a well-established cohort of drug users, in the Bronx, in New York. The study aims to elucidate pathogenetic correlates of epidemiologically defined patterns of disease progression, emphasizing the effects of drug use and bacterial infections. We will build on our previous work on the clinical spectrum of HIV, co-infections, predictors of AIDS and rate of progression, correlates of CD4% decline, mortality, and trends in drug use behaviors. We will expand laboratory assessment to include viral load, immune activation markers, cytokines, HLA typing and, for seronegative high risk drug users, correlates of protective immunity (infectibility, chemokines, CD8 suppression). Since 6/85 we have enrolled 1395 drug users (40.6% HIV seropositive) of whom 207 (14.8%) have died and 984 (82.8%) remain active as of 9/95. For this proposal we will follow 488 HIV seropositive and 455 HIV seronegative drug users. At semi-annual visits, all participants undergo standardized behavioral interviews, medical histories, directed physical exams, and venipuncture for laboratory assays and storage of specimens in repository. A disease surveillance team actively monitors hospitalizations and out-patient visits and applies standard criteria to determine all clinical endpoints. Continued study of this cohort is needed to increase the number of cases of clinical AIDS and other HIV-related endpoints (ie. infections, non-progression, and long-term survivorship) and to study disease progression and changing manifestations of disease with advances in HIV treatment regimes. With HIV seronegative drug users, we will distinguish effects of drug use from findings related to HIV, study protective immunity, and study trends in drug using behaviors in relation to the HIV epidemic. We have established collaborations with basic scientists at Johns Hopkins University (Drs. Joseph Margolic and Homayoon Farzadegan) and University of Alabama (Drs. Richard Kaslow and George Shaw) to integrate epidemiologic, immunologic, virologic, and genetic expertise to advance our knowledge of HIV pathogenesis and disease progression in drug users.